Urgent Matters Webinar Series
Improving Sepsis Care in Emergency Department
September 22, 2015
Information Release Date: May 5, 2015
Termination Date: May 5, 2016
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The George Washington University School of Medicine and Health Sciences is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
The George Washington University School of Medicine and Health Sciences designates this live internet activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Instructions for Obtaining Credit
At the end of this webinar, you will receive an email for completing the online course evaluation. Your certificate of credit will be available immediately after you complete the evaluation.
Information In accordance with the Accreditation Council for Continuing Medical Education's Standards for Commercial Support, The George Washington University Office of C ontinuing Education in the Health Professions (CEHP) requires that all individuals involved in the development and presentation of CME activity content disclose any relevant financial relationships with commercial interest(s). CEHP identifies and resolves all conflicts of interest prior to an individual’s participation in an educational activity
The following faculty, planners, and staff report that they have nor relevant financial relationships with commercial interest(s):
David Gaieski (Speaker) JessePines (Course Director) Danielle Lazar (Staff)
Molly Benoit (Staff)
LeticiaHall(Staff)
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This activity received no commercial support
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Thank You For Participating!
The George Washington University School of Medicine and Health Sciences is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
The George Washington University School of Medicine and Health Sciences designates this live internet activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
You will receive an email with an evaluation following this program, when you complete this evaluation you will be taken to a website with instructions for claiming your CME.
This program was recorded and will be posted on the Urgent Matters Website with the slides
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FOLLOW URGENT MATTERS
Sepsis:
“What’s the problem?
What’s the solution?”
David F. Gaieski, MD, FACEP Associate Professor, Department of Emergency Medicine
Vice Chair for Resuscitation Services Director of Emergency Critical Care
Sidney Kimmel Medical College Thomas Jefferson University
September 22th, 2015
Disclosures
• Bard Medical Division—research
funding to investigate temperature
burden in patients with severe sepsis
• No other relevant sepsis-related
disclosures
Outline
• SEP-1: Overview
• A case: Initial Presentation
• The Continuum of Sepsis
• Our case: Changing Severity
• Goals of Resuscitation
• Epidemiology of Sepsis
Outline (continued)
• EGDT
• Need for Early Recognition: – SIRS, Lactate, Time to Antibiotics
• Modifying EGDT: Protocolized Care in 2015
• Preventing Readmissions
• Case: Conclusion
“Except on few occasions, the
patient appears to die from the
body’s response to infection rather
than from…[the infection itself….]”
Sir William Osler, 1904
SEP-1: Overview
SEP-1
• Not a talk about implementing SEP-1
• Goal: Efficient, effective, timely care
• Acknowledges “burden of severe sepsis”
• If 2 SIRS, infection, organ dysfxn, then…
• 3 Hour Goals
– Lactate, blood cultures, antibiotics, fluid
• 6 Hour Goals
– Repeat lactate, vasopressors, assessment of
volume status, tissue perfusion
A Case: Initial Presentation
Case Vignette
• 54 year-old male
• PMHx: HTN, PAF, HL, and OA
• Chief complaint: abdominal pain
• Began 3 days ago after eating dinner, stuttering since then, becoming more severe/constant about 6 hours before presentation
• Fever to 101.5°F, 4 hours prior, treated w/ acetaminophen; two days nausea; one episode of vomiting earlier today
Case Vignette
• Allergies: NKDA
• Medications: ASA, metoprolol, amlodipine, simivastatin
• Triage VS: Tº, 100.5°F; BP, 128/78 mm Hg; HR, 88 beats per minute; RR, 21 breaths per minute; and O2 sat, 96% on RA; pain, 6/10
• Triaged as ESI 3 patient, and asked to wait in the waiting room along with 15 other patients waiting to be seen
Our patient. Next steps?
• Patient waits to be seen
• Other easily obtainable data that could help clarify the urgency of initiating treatment?
• What if serum lactate is 1.4 mmol/L?
• What if it is 4.1 mmol/L?
• EMR algorithm utilizes CC + VS to generate an automatic order for a serum lactate
• Drawn by EMT 10 minutes after triage
• Sent to the critical care laboratory for analysis
Challenge of sepsis patients
• This is a typical sepsis patient
• Why sepsis? – Presumed infection (likely intra-abdominal process) +
inflammatory response (fever, tachypnea)
• Challenge for clinicians: – How sick is he?
– Does he have a time-sensitive infection?
– How aggressive does his treatment need to be?
• On initial presentation: – no obvious signs of end organ dysfunction
– Does not obviously have severe sepsis
– What does this mean?
The Continuum of Sepsis
The Continuum of Sepsis
Sepsis SIRS Severe Sepsis Septic Shock
The Continuum of Sepsis
Sepsis SIRS Severe Sepsis Septic Shock
The Continuum of Sepsis
Sepsis SIRS Severe Sepsis Septic Shock
The Continuum of Sepsis
Sepsis SIRS Severe Sepsis Septic Shock
The Continuum of Sepsis
Bone et al. Chest 1992
Sepsis SIRS Severe Sepsis
Systemic Inflammatory Response Syndrome
SIRS criteria
• Temp < 96.8° or > 100.4° F
• HR > 90
• RR > 20 or PCO2 < 32
• WBC < 4 or > 12 or bands > 10%
Septic Shock
The Continuum of Sepsis
Sepsis SIRS Severe Sepsis Septic Shock
Systemic Inflammatory Response to Infection
• Suspected or confirmed infection
• 2 or more SIRS criteria
Bone et al. Chest 1992
The Continuum of Sepsis
Sepsis SIRS Severe Sepsis Septic Shock
Sepsis plus Organ Dysfunction
• Elevated Creatinine
• Elevated INR
• Altered Mental Status
• Elevated Lactate
• Hypotension that responds to fluid
Levy et al. Crit Care Med; 2003
The Continuum of Sepsis
Sepsis SIRS Severe Sepsis Septic Shock
Severe Sepsis and Hypotension
• Hypotension that does NOT respond to fluid (30 cc/kg bolus)
Bone et al. Chest, 1992
Rivers et al. NEJM, 2001
Cryptic Shock
•Normotensive
•Lactate > 4
Our Case: Changing Severity
Patient Vignette
• Lactate (15 minutes after sent)= 5.4 mmol/L
• Immediately brought back to a treatment room
• 2 18 gauge IVs placed
• 3 L NSS were infused in 1 hr
• WBC=16.5; HCO3-=18; Tbili=2.7; Alk phos=235; AST/ALT 335/284; lipase 650
Patient Vignette
• Repeat VS: BP 128/82; HR 84; RR 24
• Bedside ultrasound: – Gallstones
– GBWT
– Dilated intrahepatic ducts
• Bedside ECHO: – Under-filled RV
– > 50% IVC collapse
• Continue volume resuscitation
• Close monitoring
Goals of Resuscitation
Initial Management
IV access
Fluid resuscitation
Supplemental oxygen
Cardiac monitoring
Labs, cultures, CXR
Antibiotics
Is the patient in shock?
Goals of Interventions for Shock
• Stabilize patient
• Eradicate source of infection
• Restore perfusion
• Modulate body’s inflammatory and
anti-inflammatory responses
• Cessation of ongoing lactate
production
Epidemiology of Sepsis
Why is this so Important?
• A patient a minute presents to a US ED
• 750,000 cases/yr of severe sepsis in USA
• 215,000 deaths/yr directly related to sepsis
• Tenth leading cause of death in USA
• Rate of sepsis cases is increasing faster than the population
• 37% of severe sepsis patients come through the ED
Wang et al. Crit Care Med, 2007
Angus et al. Crit Care Med, 2001
Underestimate?
• “Benchmarking the incidence and mortality of
severe sepsis in the United States”
• NIS: Nationally representative sample
• 4 previously validated capture techniques
(Angus, Wang, Dobrovskii, Martin)
• All utilize ICD 9 codes (+/- sepsis codes)
• Annual incidence and mortality from severe
sepsis
Gaieski et al, CCM, 2013
Gaieski et al, CCM, 2013
Gaieski et al, CCM, 2013
Kaukonen, JAMA, 2014
Early Goal-Directed Therapy
Negative Trials in the 80s and 90s
• High dose methylprednisolone
• NSAIDs
• Anti-LPS
• TNF receptor antagonists
• GOT
• Shared features: – ICU initiated
– 24 hours or more to enrollment
– Non-selective interventions
A new approach was needed…
Critical Care
• Critical care is a concept
not a location
• It is a way of treating patients that
begins in the pre-hospital setting with
EMS care, continues in the ED, and is
completed in the ICU
Safar P. Critical care medicine---quo vadis? CCM. 1974;2:1-5
Early Goal-Directed Therapy
(EGDT)
Rivers et al. NEJM, 2001
Algorithmic
EGDT Mortality
46.5%
30.5%
49.0%
33.3%
56.9%
44.3%
0.0%
10.0%
20.0%
30.0%
40.0%
50.0%
60.0%
In House 28-Day 60-Day
Standard
EGDT
Rivers et al NEJM, 2001
Need for Early Recognition
Systemic Inflammatory Response System
(SIRS) Criteria
Breaking down initial detection
• How helpful are the SIRS criteria?
3
710
17 16
20
46
0
10
20
30
40
50
No SIRS SIRS 2 SIRS 3 SIRS 4 Sepsis Severe
Sepsis
Septic
Shock
RANGEL-FRAUSTO JAMA 1995
Mort
alit
y, %
Mortality in Admitted Patients
SIRS, Severe Sepsis
• Historically, SIRS=>very sensitive; but not
specific
• Shapiro: SIRS neither sensitive nor specific
• 3102 pts, suspected infection (blood culture
drawn) – 34% (420/1219) severe sepsis pts didn’t meet SIRS criteria
– 24% (13/54) septic shock pts didn’t meet SIRS criteria
Shapiro et al, Ann Emerg Med 2006
• 172 ICUs in Australia, New Zealand
• 109,663 severe sepsis patients
– 87.9% SIRS-positive
– 12.1% SIRS-negative
• “The need for two or more SIRS
criteria…excluded one in eight otherwise
similar patients with infection, organ failure,
and substantial mortality…”
Kaukonen et al. NEJM, 2015
Kaukonen et al. NEJM, 2015
Lactate
Utilizing Lactate
Liver: Cori Cycle
PDH
Thiamine
Lactate Production
X
Cori
Cycle
• Hypothesis
– Lactate measured on ED presentation is associated with mortality and risk stratifies severe sepsis patients INDEPENDENT of blood pressure
• 831/856 (97%) of admitted severe sepsis pts had lactate sent
– Median lactate=2.9 mmol/L
– 28 day mortality: 22.7%
• Divided into:
– Low: ≤ 2mmol/L
– Medium: > 2 to ≤ 3.9mmol/L
– High: ≥ 4mmol/L
• Stratified to presence or absence of refractory hypotension
Mikkelsen et al. Crit Care Med, 2009
ED Lactate in Severe Sepsis
Lactate (mmol/L)
Mo
rta
lity (
%)
Mikkelsen et al. CCM. 2009
ED Lactate in Severe Sepsis
Lactate (mmol/L)
Mo
rta
lity (
%)
Mikkelsen et al. CCM. 2009
Patient Vignette (cont’d)
• A-line placed in L femoral artery
• CVC placed in the R IJ vein under ultrasound guidance – initial CVP: 6 mmHg, MAP: 55 mmHg, initial
ScvO2: 38%
• Further fluid boluses
• After 4 L NSS was infused – CVP: 12 mmHg
– MAP: 59 mmHg
– ScvO2: 45%
Patient Vignette (cont’d)
• Input: 4550cc; Output 20cc
• Repeat ECHO: – Decreased contractility, EF 45%
– IVC collapse decreased
• Started on norepinephrine and dobutamine
• Given Vancomycin and Piperacillin-Tazobactam with 1st antibiotic started 50 minutes after triage
Does that matter?
Time to Antibiotics
Time to Antibiotics
• Design – Retrospective cohort study of 14 ICUs
• Patients – 2,731 adults with septic shock
• Primary variable – Duration of hypotension prior to administration
of appropriate antimicrobial
• Primary outcome measure – Survival to hospital discharge
Kumar et al. Critical Care Medicine. 2006
Time to Antibiotic
0
10
20
30
40
50
60
70
Time 0 1 hour 2 hours 3 hours 4 hours 5 hours 6 hours
Time to Antibiotic
Mo
rta
lity
7.6% absolute increase in mortality per hour
Kumar et al. Critical Care Medicine, 2006
• To study the relationship between time to antibiotics and mortality in patients treated with EGDT in the ED
• 261 patients
• Average time to antibiotics:
– Triage to antibiotics: 119 minutes
– Qualification for EGDT to antibiotics: 42 minutes
Gaieski et al. Crit Care Med, 2010
Time Qual for EGDT to
Appropriate Antibiotics
0
5
10
15
20
25
30
35
40
45
< 1 hour < 2 hour < 3 hour
25.2
28.4 28.7
38.6 40.4
44.7
Inp
ati
en
t M
ort
alit
y (
%)
Antibiotic Timing
Goal Delayed
Gaieski et al. CCM, 2010
Broad-Spectrum Antimicrobials:
+ Cefepime 1 gm IV (1)
+ Vancomycin 1 gm (≤ 70 kg) or
1.5 gm (> 70 kg) IV
± Amikacin 15 mg/kg or
7.5 mg/kg (CrCl < 20) IV (4)
PCN
Allergy
Broad-Spectrum Antimicrobials:
+ Levofloxacin 750 mg IV
+ Vancomycin 1 gm (≤ 70 kg) or
1.5 gm (> 70 kg) IV
± Amikacin 15 mg/kg or
7.5 mg/kg (CrCl < 20) IV (4)
Community Acquired Pneumonia: + Azithromycin 500mg IV (2)
Anaerobic Source: + Metronidazole 500 mg IV (3)
On TPN: + Fluconazole 400 mg IV
Prolonged Neutropenia ±
Steroids:
+ Caspofungin 70 mg IV
± Hydrocortisone 50-100 mg IV
Yes No
Gaieski et al. CCM, 2011
Modifying EGDT
• Protocol-driven sepsis care lowers mortality
• EGDT underutilized
• What factors are associated with not initiating
EGDT in ED?
• 340 EGDT-eligible patients
• EGDT not initiated in 142 pts (42%)
Mikkelsen et al. Chest, 2010
Mikkelsen et al. Chest, 2010
4 Risk Factors Associated with Non-
adherence
• Female patient (p=0.001)
• Female physician (p=0.041)
• Lactate as qualifying criterion (p=0.018)
• Skin infections or urinary tract infections
• Non-consultation of severe sepsis
service (p<0.001)
Mikkelsen et al. Chest, 2010
Protocolized Care
• 2013, protocolized care = standard of care
• Objective interventions/Objective endpoints
• Goal: differentiate Responders from Non-Responders @ each stage of resuscitation
• Potential Organ Dysfunction Immediate attention regardless of patient location in health care system
• EGDT most famous type of protocolized care
• New insights arrive…
The ProCESS Trial
• Three arms:
1.Protocol-based EGDT
2.Protocol-based standard therapy Similar to # 1 but no mandated CVC, transfusion only
for Hgb<7.5, fluids only to “volume repleted”, no specific pressor mandates
3.“Usual care” (clinician’s preference)
ProCESS
• 51 ICUs in Australia and New Zealand
• 1600 patients presenting to the ED in early
septic shock
• 2 SIRS, source of infection, hypotension or
hypoperfusion
• Antibiotics prior to randomization
• Randomized to EGDT vs. usual care
ARISE Investigators. NEJM, 2015
ARISE
ARISE Investigators. NEJM, 2015
ProMISe
Mouncey et al. NEJM, 2015
Preventing Readmissions
Post-Discharge Problems
• “Unfortunately, discharge from a severe
sepsis hospitalization is all too often the
beginning of the end”
• Iwashnya and colleagues:
– the 3-year case-fatality rate remains
stubbornly above 70%
– Readmissions common
– Costs are staggering
Buchmann, “You Tell Me.” CCM, 2015
Readmissions @ Penn
• Patients admitted with septic shock (serum
lactate ≥ 4 mmol/L or refractory hypotension)
and discharged alive to a non- hospice
setting between 2007 and 2010
• 269 at-risk survivors:
– 63 (23.4%; 95% CI, 18.2–28.5) were readmitted
within 30 days of discharge
– 12 (4.5%; 95% CI, 2.3–7.7) returned to the ED for
a treat-and-release visit
Ortego et al. CCM, 2015
Readmissions @ Penn
• 75% of readmissions occurred within
15 days of discharge:
– more likely in oncology pts (p = 0.001)
– pts with a longer hospital LOS (p = 0.04)
– 16% resulted in death or d/c to hospice
– Potentially related to the index septic shock
hospitalization in 78% (49/63) of cases
– 46% of readmissions were infection-related
Ortego et al. CCM, 2015
Case Conclusion
• Evaluated by ESS
• Went to IR for a percutaneous drain
• E. coli in blood cultures and drainage fluid
• On NE and DOBUT for 3 days
• Clinically stabilized
• Delayed cholecystectomy
• Discharged in good condition on HD-17
Conclusions-1
• Osler was right—the patient dies as much from the body’s response to infection as from the infection itself
• Huge epidemiologic burden of sepsis
• Recognition: major hurdle
• SIRS: Helpful but not infallible
• Lactate: marker for critical illness and powerful screening tool
Conclusions-2
• Protocolized care improves outcomes
• Modify to fit different resource settings
• Antibiotics: – integrate into early resuscitation strategies
– prioritize along w/ other aspects of initial critical care
• Rivers’ fundamental insight: – moving aggressive, protocolized care to the most
proximate phase of critical illness
• The optimal details remain to be elucidated
• SEP-1 adherence should further improve care